001453581 000__ 05906cam\a2200577\a\4500 001453581 001__ 1453581 001453581 003__ OCoLC 001453581 005__ 20230314003434.0 001453581 006__ m\\\\\o\\d\\\\\\\\ 001453581 007__ cr\un\nnnunnun 001453581 008__ 221217s2023\\\\si\\\\\\ob\\\\000\0\eng\d 001453581 019__ $$a1354993787 001453581 020__ $$a9789811978142$$q(electronic bk.) 001453581 020__ $$a981197814X$$q(electronic bk.) 001453581 020__ $$z9811978131 001453581 020__ $$z9789811978135 001453581 0247_ $$a10.1007/978-981-19-7814-2$$2doi 001453581 035__ $$aSP(OCoLC)1355218110 001453581 040__ $$aEBLCP$$beng$$cEBLCP$$dGW5XE$$dYDX$$dUKAHL 001453581 049__ $$aISEA 001453581 050_4 $$aQP623.8.P75 001453581 08204 $$a572/.633$$223/eng/20230104 001453581 1001_ $$aByun, Wan Gi. 001453581 24510 $$aDiscovery of small-molecule modulators of protein-RNA interactions for treating cancer and COVID-19 /$$cWan Gi Byun. 001453581 260__ $$aSingapore :$$bSpringer,$$c2023. 001453581 300__ $$a1 online resource (156 p.). 001453581 4901_ $$aSpringer Theses 001453581 500__ $$a"Doctoral thesis accepted by Seoul National University, Seoul, Korea (Republic of)" 001453581 504__ $$aIncludes bibliographical references. 001453581 5050_ $$aIntro -- Supervisor's Foreword -- Abstract -- Acknowledgements -- Contents -- List of Figures -- List of Tables -- List of Schemes -- 1 Introduction -- 1.1 Protein-RNA Interaction -- 1.2 Therapeutic Potentials of Modulating PRI -- 1.3 Chemical Biology Approaches for the Discovery of PRI Modulator -- 1.4 Aims and Scope of the Thesis -- References -- 2 Identification of Small-Molecule Inhibitors of Oncogenic Lin28-Let-7 Interaction -- 2.1 Discovery of a Small-Molecule Inhibitor of Protein-microRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28 -- 2.1.1 Introduction 001453581 5058_ $$a2.1.2 Results and Discussion -- 2.1.3 Conclusion -- 2.1.4 Experimental Section -- 2.2 Restoring Let-7 MicroRNA Biogenesis Using a Small-Molecule Inhibitor of the Protein-RNA Interaction -- 2.2.1 Introduction -- 2.2.2 Results and Discussion -- 2.2.3 Conclusion -- 2.2.4 Experimental Section -- References -- 3 Discovery of Small-Molecule Modulators of Protein-RNA Interactions by Fluorescence Intensity-Based Binding Assay -- 3.1 Introduction -- 3.2 Results and Discussion -- 3.2.1 Construction of a Fluorescence Intensity-Based Lin28-Let-7 Binding Assay 001453581 5058_ $$a3.2.2 Discovery of a New Class of Small-Molecule Inhibitors of the Lin28-Let-7 Interaction -- 3.2.3 Construction of a Fluorescence Intensity-Based Assay to Monitor Roquin-Tnf CDE Interaction -- 3.3 Conclusion -- 3.4 Experimental Section -- 3.4.1 Protein Expression and Purification -- 3.4.2 Fluorescence Intensity-Based Binding Assays -- 3.4.3 Electrophoretic Mobility Shift Assay (EMSA) -- 3.4.4 RNA Sequences -- 3.4.5 TaqMan MiRNA Assay-Based QRT-PCR -- 3.4.6 Cell Culture -- 3.4.7 Western Blot -- 3.4.8 Chemistry -- 3.4.9 Purity Determination from HPLC Analysis 001453581 5058_ $$a3.4.10 Synthetic Procedures and Spectroscopic Data -- References -- 4 Harnessing Stress Granule Formation by Small Molecules to Inhibit the Cellular Replication of SARS-CoV-2 -- 4.1 Introduction -- 4.2 Results and Discussion -- 4.2.1 Identification of Small-Molecule Enhancers of Stress Granule Formation and Their Cellular Antiviral Activities -- 4.2.2 Inhibition of the Cellular Replication of SARS-CoV-2 by the Stress Granule Enhancers -- 4.3 Conclusion -- 4.4 Experimental Section -- 4.4.1 Chemistry -- 4.4.2 Purity Determination from HPLC Analysis -- 4.4.3 Cell Culture and Transfection 001453581 5058_ $$a4.4.4 Western Blot -- 4.4.5 Stress Granule Imaging by Immunofluorescence -- 4.4.6 Stress Granule Monitoring and Compound Screening Using G3BP1-GFP Expressed U2OS Cell Line -- 4.4.7 Cell Viability Assay -- 4.4.8 RNA Extraction and Quantitative Real-Time PCR -- 4.4.9 Virus -- 4.4.10 Antiviral Test and Dose-response Curve (DRC) Analysis by Immunofluorescence -- 4.4.11 Co-Immunofluorescence -- 4.4.12 Drug Combination Assay -- 4.4.13 Spectroscopic, Mass & HPLC Purity Data -- References -- Appendix 001453581 506__ $$aAccess limited to authorized users. 001453581 520__ $$aThis book describes the development of novel proteinRNA-binding assays and their applications in a high-throughput manner for the identification of small-molecule modulators of proteinRNA interactions to treat cancer and COVID-19. Modulating proteinRNA interactions with small molecules is expected to provide novel biological insights of the interrelation of diseases with the proteinRNA interactome. The modulations may also be exploited therapeutically. For these reasons, the development of a simple, reliable, and sensitive proteinRNA-binding assay is necessary for high-throughput screening to discover new effective chemical entities capable of acting on diverse proteinRNA interactions. This book discusses the discovery of small-molecule modulators targeting proteinRNA interactions that are potentially valuable to treat cancer and COVID-19 by constructing novel high-throughput screening methods. The results of this dissertation provide valuable insights into the regulation of proteinRNA interactions in chemical biology and drug development. 001453581 588__ $$aOnline resource; title from PDF title page (SpringerLink, viewed January 4, 2023). 001453581 650_0 $$aRNA-protein interactions. 001453581 650_0 $$aCancer$$xGenetic aspects. 001453581 650_0 $$aCancer$$xMolecular aspects. 001453581 650_0 $$aCOVID-19 (Disease)$$xGenetic aspects. 001453581 650_0 $$aCOVID-19 (Disease)$$xMolecular aspects. 001453581 655_0 $$aElectronic books. 001453581 77608 $$iPrint version:$$aByun, Wan Gi$$tDiscovery of Small-Molecule Modulators of Protein-RNA Interactions for Treating Cancer and COVID-19$$dSingapore : Springer,c2022$$z9789811978135 001453581 830_0 $$aSpringer theses. 001453581 852__ $$bebk 001453581 85640 $$3Springer Nature$$uhttps://univsouthin.idm.oclc.org/login?url=https://link.springer.com/10.1007/978-981-19-7814-2$$zOnline Access$$91397441.1 001453581 909CO $$ooai:library.usi.edu:1453581$$pGLOBAL_SET 001453581 980__ $$aBIB 001453581 980__ $$aEBOOK 001453581 982__ $$aEbook 001453581 983__ $$aOnline 001453581 994__ $$a92$$bISE